Mechanical regulation of bone remodeling

Wang, Lijun; You, Xiuling; Zhang, Lingli; Zhang, Changqing; Zou, Weiguo

doi:10.1038/s41413-022-00190-4

Cited by 236 publications

(170 citation statements)

References 241 publications

(331 reference statements)

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“…β = 0). It is then worth noticing that osteoporosis, including the effects experienced by astronauts involved in medium/long-term space flights due to microgravity conditions [32,95], has been recently demonstrated to be associated to a progressive reduction of the osteon overall anisotropy ratio with respect to healthy bones, combined with a decrease of the level of mineral bone density. This can reach a critical condition of an only partially reversible recovery of the bone's physiological status, for which the behaviour of the osteon tends to finally become isotropic [48,53,96].…”

Section: Discussionmentioning

confidence: 99%

Toughening and mechanosensing in bone: a perfectly balanced mechanism based on competing stresses

Fraldi¹,

Cutolo²,

Carotenuto³

et al. 2022

Preprint

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Bone is a stiff and though, hierarchically organized and continuously evolving material that optimizes its structure across the scales to properly respond to mechanical stimuli, which also govern growth and remodelling processes through a complex cascades of interlaced mechanobiological events. However, a full understanding of the fascinating underlying mechanisms responsible for the cooperation of bone toughness and biological functions, with important implications in bone ageing, osteoporosis and post-trauma repairing processes, has yet to be achieved. In particular, how micro-damage nucleation -which is necessary for tissue remodelling-does not evolve into catastrophic failure in such a stiff material, still remains a partial enigma, given that the presence of cement lines, interfaces and sacrificial elements, which dissipate energy and deviate cracks, alone do not provide a definitive answer to the question. To help solve this challenging problem, here we bring to light a novel stress-based bone toughening mechanism, calling into play the nearly-symmetrical, chiral and hierarchical architecture of the osteon, in which adjacent lamellae are arranged in clockwise and counter-clockwise manners as a result of the different orientation of their components, i.e. collagen fibrils and carbonated hydroxyapatite crystallites. Somewhat counter-intuitively, we demonstrate that this arrangement simultaneously gives rise to stress states that are alternating in sign along the osteon radius and to localized stress amplification phenomena, both in the tensile and compressive regimes. This unveils a previously unforeseen synergistic mechanism allowing micro-damage accumulation without propagating cracks, which is kindled by the contrast between crack-opening due to tensile hoop stresses (required for bone remodelling)

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Section: Discussionmentioning

confidence: 99%

Toughening and mechanosensing in bone: a perfectly balanced mechanism based on competing stresses

Fraldi¹,

Cutolo²,

Carotenuto³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…However, BMAs could also interfere with skeletal homeostasis and bone remodeling via its metabolic activities ( 57 ). The maintenance of bone mass depends on the dynamic and precise coordination of osteoclast-dominated bone resorption and osteoblast-mediated bone formation ( 58 , 59 ). Studies in rats and dogs indicated reduced osteoblast activity, osteoclast numbers and increased bone loss at sites with higher BMA numbers ( 57 ).…”

Section: Metabolic Featuresmentioning

confidence: 99%

Distinct Metabolism of Bone Marrow Adipocytes and their Role in Bone Metastasis

Cao

Gaculenko

et al. 2022

Front. Endocrinol.

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Bone marrow adipocytes (BMAs) represent 10% of the total fat mass of the human body and serve as an energy reservoir for the skeletal niche. They function as an endocrine organ by actively secreting fatty acids, cytokines, and adipokines. The volume of BMAs increases along with age, osteoporosis and/or obesity. With the rapid development of multi-omic analysis and the advance in in vivo imaging technology, further distinct characteristics and functions of BMAs have been revealed. There is accumulating evidence that BMAs are metabolically, biologically and functionally unique from white, brown, beige and pink adipocytes. Bone metastatic disease is an uncurable complication in cancer patients, where primary cancer cells spread from their original site into the bone marrow. Recent publications have highlighted those BMAs could also serve as a rich lipid source of fatty acids that can be utilized by the cancer cells during bone metastasis, particularly for breast, prostate, lung, ovarian and pancreatic cancer as well as melanoma. In this review, we summarize the novel progressions in BMAs metabolism, especially with multi-omic analysis and in vivo imaging technology. We also update the metabolic role of BMAs in bone metastasis, and their potential new avenues for diagnosis and therapies against metastatic cancers.

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“…The two matrix components make bone a composite material with outstanding mechanical properties, but this comes with a caveat: bone needs to be modeled and remodeled during growth and adult life, respectively, otherwise its mechanical properties degrade over time, as is the case for elderly individuals of both genders and for some bone genetic diseases [3,4] . Proper bone modeling/remodeling is guaranteed by a finely tuned balance among the three main bone cells: osteoblasts, the bone-forming cells; osteoclasts, the bone-resorbing cells; and osteocytes, key controllers of bone matrix homeostasis [5,6] . During bone modeling, all bone sections change shape following both mechanical cues and microenvironmental factors and expand to accommodate the growing organism in physiological conditions.…”

Section: Normal Bone Physiology: Cellular Players and The "Virtuous C...mentioning

confidence: 99%

Liquid biopsies in primary and secondary bone cancers

Ucci¹,

Rucci²,

Ponzetti³

2022

Cancer Drug Resist

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Liquid biopsies are a powerful tool to non-invasively analyze tumor phenotype and progression as well as drug resistance. In the bone oncology field, liquid biopsies would be particularly important to develop, since standard biopsies can be very painful, dangerous (e.g., when found in proximity to the spinal cord), and hard to collect. In this review, we explore the recent advances in liquid biopsies in both primary (osteosarcoma and Ewing sarcoma) and secondary bone cancers (breast, prostate, and lung cancer-induced bone metastases), presenting their current role and highlighting their unexpressed potential, as well as the barriers limiting their possible adoption, including costs, scalability, reproducibility, and isolation methods. We discuss the use of circulating tumor cells, cell-free circulating tumor DNA, and extracellular vesicles for the purpose of improving diagnosis, prognosis, evaluation of therapy resistance, and driving therapy decisions in both primary and secondary bone malignancies.

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Mechanical regulation of bone remodeling

Cited by 236 publications

References 241 publications

Toughening and mechanosensing in bone: a perfectly balanced mechanism based on competing stresses

Toughening and mechanosensing in bone: a perfectly balanced mechanism based on competing stresses

Distinct Metabolism of Bone Marrow Adipocytes and their Role in Bone Metastasis

Liquid biopsies in primary and secondary bone cancers

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